Loss of microbial diversity and pathogen domination of the gut microbiota in critically ill patients

Ray, Anuradha; Halstead, Fenella D.; Bamford, Amy; Casey, Anna; Thomson, Nicholas M.; Schaik, Willem van; Snelson, Catherine; Goulden, Robert; Foster-Nyarko, Ebenezer; Savva, George M.; Whitehouse, Tony; Pallen, Mark J.; Oppenheim, Beryl

doi:10.1099/mgen.0.000293

Cited by 75 publications

(69 citation statements)

References 77 publications

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“…With the growing use of MAG methods in infectious disease research [73][74][75][76][77] and the public-health and agrifood importance of the LGT of AMR and VF genes, we also specifically evaluated the binning of these gene classes. The majority of these genes were correctly assembled across assemblers, but were either not assigned or incorrectly assigned to MAG bins during binning.…”

Section: Discussionmentioning

confidence: 99%

Metagenome-assembled genome binning methods with short reads disproportionately fail for plasmids and genomic Islands

et al. 2020

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Metagenomic methods enable the simultaneous characterization of microbial communities without time-consuming and bias-inducing culturing. Metagenome-assembled genome (MAG) binning methods aim to reassemble individual genomes from this data. However, the recovery of mobile genetic elements (MGEs), such as plasmids and genomic islands (GIs), by binning has not been well characterized. Given the association of antimicrobial resistance (AMR) genes and virulence factor (VF) genes with MGEs, studying their transmission is a public-health priority. The variable copy number and sequence composition of MGEs makes them potentially problematic for MAG binning methods. To systematically investigate this issue, we simulated a low-complexity metagenome comprising 30 GI-rich and plasmid-containing bacterial genomes. MAGs were then recovered using 12 current prediction pipelines and evaluated. While 82–94 % of chromosomes could be correctly recovered and binned, only 38–44 % of GIs and 1–29 % of plasmid sequences were found. Strikingly, no plasmid-borne VF nor AMR genes were recovered, and only 0–45 % of AMR or VF genes within GIs. We conclude that short-read MAG approaches, without further optimization, are largely ineffective for the analysis of mobile genes, including those of public-health importance, such as AMR and VF genes. We propose that researchers should explore developing methods that optimize for this issue and consider also using unassembled short reads and/or long-read approaches to more fully characterize metagenomic data.

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Section: Discussionmentioning

confidence: 99%

Metagenome-assembled genome binning methods with short reads disproportionately fail for plasmids and genomic Islands

et al. 2020

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“…With the growing use of MAG methods in infectious disease research (e.g., [51,52,53,54,55]) and the public-health importance of the LGT of AMR and VF genes, we also speci cally evaluated the binning of these gene classes. The majority of these genes were correctly assembled across assemblers but were either not assigned or incorrectly assigned to MAG bins during binning.…”

Section: Discussionmentioning

confidence: 99%

Metagenome-Assembled Genome Binning Methods with Short Reads Disproportionately Fail for Plasmids and Genomic Islands

Maguire

Jia²,

Gray³

et al. 2020

Preprint

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MotivationMetagenomic methods have emerged as a key tool in public-health microbiology for surveillance of virulence factor (VF) and antimicrobial resistance (AMR) genes. However, metagenomic data, even when assembled, typically results in complex, mixed sets DNA sequence fragments rather than fully resolved individual genomes. Recently, metagenome-assembled genomes (MAGs) have emerged as a promising approach that groups sequences into bins that are likely derived from the same underlying genome. However, MAGs have not been well assessed for their ability to identify some of the key sequences of interest for infectious disease surveillance purposes: AMR and VFs associated with mobile genetic elements (MGEs) such as plasmids and genomic islands (GIs). We hypothesized that due to the di erent copy number and sequence composition of plasmids and GIs compared to core genome sequence, such sequences will be under-represented in MAG-based approaches. ResultsTo evaluate the impact of MAG recovery methods on recovery of AMR genes and MGEs, we generated a simulated metagenomic dataset comprised of 30 genomes with up to 16.65% of the chromosomal DNA consisting of GIs and 65 associated plasmids. MAGs were then recovered from this data using 12 di erent MAG pipelines and evaluated for recovery accuracies. Across all pipelines, 81.9-94.3% of chromosomes were recovered and binned. However, only 37.8-44.1% of GIs and 1.5-29.2% of plasmids were recovered and correctly binned at >50% coverage. In terms of AMR and VF genes associated with MGEs, 0-45% of GI-associated AMR genes and 0-16% of GI-associated VF genes were correctly assigned. More strikingly, 0% of plasmid-borne VF or AMR genes were recovered. This work shows that regardless of the MAG recovery approach used, plasmid and GI dominated sequences will disproportionately be left unbinned or incorrectly binned. From a public-health perspective, this means MAG approaches are less suited for analysis of mobile genes, especially key groups such as AMR and VF genes. This underlines the utility of read-based and long-read approaches to thoroughly evaluate the resistome in metagenomic data.

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“…or yeasts such as Candida spp. ended up being the dominant microorganisms in the gut [19,20]. Furthermore, the extent of the alteration of the microbiota could be linked to mortality.…”

Section: Plos Onementioning

confidence: 99%

Relationship between the composition of the intestinal microbiota and the tracheal and intestinal colonization by opportunistic pathogens in intensive care patients

et al. 2020

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Infections caused by multidrug-resistant Gram-negative bacilli (MDR-GNB) are a major issue in intensive care. The intestinal and oropharyngeal microbiota being the reservoir of MDR-GNB. Our main objective was to assess the link between the composition of the intestinal microbiota and the tracheal and intestinal colonization by MDR-GNB, and also by Enterococcus spp. and yeasts. Methods We performed a 2-month prospective, monocentric cohort study in the medical intensive care unit of our hospital. Patients ventilated >3 days and spontaneously passing feces were included. A fecal sample and an endotracheal aspiration (EA) were collected twice a week. MDR-GNB but also Enterococcus faecium and yeasts (as potential dysbiosis surrogate markers) were detected by culture methods. The composition of the intestinal microbiota was assessed by 16S profiling. Results We collected 62 couples of feces and EA from 31 patients, including 18 feces and 9 EA positive for MDR-GNB. Forty-eight fecal samples were considered for 16S profiling. We did not observe a link between the diversity and the richness of the intestinal microbiota and the MDR-GNB intestinal relative abundance (RA). Conversely, we observed a negative link between the intestinal diversity and richness and the RA of Enterococcus spp. (p<0.001). Conclusion The fecal MDR-GNB RA was not associated to the diversity nor the richness of the intestinal microbiota, but that of Enterococcus spp. was.

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Loss of microbial diversity and pathogen domination of the gut microbiota in critically ill patients

Cited by 75 publications

References 77 publications

Metagenome-assembled genome binning methods with short reads disproportionately fail for plasmids and genomic Islands

Metagenome-assembled genome binning methods with short reads disproportionately fail for plasmids and genomic Islands

Metagenome-Assembled Genome Binning Methods with Short Reads Disproportionately Fail for Plasmids and Genomic Islands

Relationship between the composition of the intestinal microbiota and the tracheal and intestinal colonization by opportunistic pathogens in intensive care patients

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